The object of the proposed study is to determine the immunologic potential of the lymphoid cells of the Peyer's patches of the mouse small intestine. Through the proposed study, data will be gained which will be useful in understanding what controls the generation and regulation of the mucosal immune response. Such information is prerequisite for the development of immunization protocols which can confer long-lasting protection in man and animals against enteric disease. The proposal presented here endeavors to determine in particular the effects that bacteria and their products, especially, bacterial lipopolysaccharide (LPS), have on the Peyer's patch immune response. This will be accomplished by investigating the Peyer's patch cell immune responsiveness of conventional mice, germ-free mice, and mice mono-associated with various members of the enteric flora. Peyer's patch cells of germ-free mice represent a cell population which has only minimal prior exposure to LPS, when compared to Peyer's patch cells from conventional mice. A comparison of the effects of LPS on the Peyer's patch cells of conventional and germ-free mice should therefore allow a definition of the role which gut-derived LPS plays in the generation of the Peyer's patch immune response. A study of the immune responsiveness of Peyer's patch cells from germ-free mice fed LPS in their drinking water should delineate the extent to which prior exposure to LPS modifies the immunologic action of LPS on Peyer's patch cells. Likewise the pre-exposure of mice to antigen by the oral or systematic route will define the extent to which the different mode of immunization can modify subsequent Peyer's patch immune responsiveness. Techniques used will include in vitro humoral antibody synthesis by Peyer's patch cells, in vitro blastogenesis, and the effects of LPS on Peyer's patch cell immune responsiveness in these systems.